Different subregions of the anterior cingulate cortex differentially regulate acute itch-scratching behavior in rats

Numerous studies in both humans and rodent models have consistently demonstrated the important role of the anterior cingulate cortex (ACC) in emotion perception, pain processing, memory formation, etc. The ACC can be anatomically subdivided into rostral and caudal subregions, each exhibiting distinct functional profiles. Previous studies have provided robust evidence supporting the involvement of the ACC as a whole in pruritus regulation; however, the specific regulatory effects exerted by the distinct subregions of the ACC on pruritus remain unknown. In this study, we investigated the impact of rostral ACC and caudal ACC neuronal intervention on scratching behavior in rats with acute experimental histaminergic and nonhistaminergic itch. The results demonstrated that activation of ACC neurons occurs during acute itching. Moreover, pharmacogenetic inhibition of the rostral ACC increased acute itch scratching induced by 5-hydroxytryptamine (5-HT), whereas inhibition of the caudal ACC reduced both 5-HT- and Compound 48/80-induced acute itch-scratching behavior. In conclusion, the rostral ACC exerts a negative modulatory effect on itch, whereas the caudal ACC plays a positive modulatory role. Both subregions are implicated in the modulation of nonhistaminergic itch, whereas only the caudal ACC is involved in the modulation of histaminergic itch.